Renal Division, Department of Internal Medicine, Ghent University Hospital, Ghent, Belgium.
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospital, Ghent, Belgium.
Nephron. 2018;140(1):63-73. doi: 10.1159/000490201. Epub 2018 Jun 25.
Thrombomodulin (TM) is an endothelial glycoprotein that is present in all blood vessels. Five percent of all patients with atypical hemolytic uremic syndrome (aHUS) have mutations in the gene coding for TM, with a peak presentation in young children. Mutations often translate into quantitative and qualitative abnormalities of this endothelial glycoprotein. Outcome of the TM-associated aHUS is relatively poor with frequent relapses after transplantation despite its membrane-bound character. We observed a woman presenting with malignant hypertension (MHT) and associated kidney, brain, cardiac, and hematological involvement with thrombotic microangiopathy on kidney biopsy. She had a documented mutation of the gene coding for TM, which was associated with both aHUS and an increased risk for venous and arterial thrombosis. As TM has anti-coagulant, anti-inflammatory, and cytoprotective properties and also attenuates alternative complement activation, this glycoprotein could play an active role in other diseases with endothelial involvement apart from aHUS. We discuss the potential role of TM in the pathophysiology of various endotheliopathies including MHT. We also provide a framework for future therapeutic options.
血栓调节蛋白（TM）是一种存在于所有血管中的内皮糖蛋白。5%的非典型溶血尿毒综合征（aHUS）患者存在编码 TM 的基因突变，其发病高峰在幼儿期。这些突变通常导致这种内皮糖蛋白的数量和质量异常。尽管 TM 相关的 aHUS 具有膜结合特性，但在移植后仍经常复发，其预后相对较差。我们观察到一名女性表现为恶性高血压（MHT），并伴有肾脏、大脑、心脏和血液学受累，肾活检显示血栓性微血管病。她有 TM 基因突变的记录，这与 aHUS 以及静脉和动脉血栓形成的风险增加有关。由于 TM 具有抗凝、抗炎和细胞保护作用，并能抑制替代补体激活，因此这种糖蛋白除了在 aHUS 之外，可能在其他涉及内皮的疾病中发挥积极作用。我们讨论了 TM 在包括 MHT 在内的各种内皮病发病机制中的潜在作用。我们还为未来的治疗选择提供了一个框架。
